Obstructive Sleep Apnea in Hypertension

Introduction About one-half of patients who have essential hypertension have obstructive sleep apnea (OSA), and about one-half of patients who have obstructive sleep apnea have essential hypertension. OSA can cause even resistant hypertension if left untreated. These two entities often co-exist and are seen as a continuum of the same process. Eighty percent to 90% of OSA cases are undiagnosed mostly because of a lack of awareness. Material and methods This was a cross-sectional study done over a period of one year in a tertiary care hospital. After taking informed consent, 179 hypertensive patients of >18 years were included in the study. All patients were screened for OSA by the STOP-BANG questionnaire. Patients having scores of ≥3 were subjected to overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). Patients with a STOP-BANG score ≤2 or score ≥3 with AHI <5, were considered non-OSA. Results More than half (53.1%) of the patients enrolled in the study had OSA. Their age ranged from 18 to 78 years and the mean age was 52.07±11.40 years. The mean age of OSA cases was found to be slightly higher than that of non-OSA. The majority of OSA cases were males (73.7%). There was an increase in the prevalence, as well as the severity of OSA, with an increase in BMI. Most of the cases had snoring and a history of tiredness. Triglyceride (TG) and low-density lipoprotein (LDL) levels of the OSA group were found to be significantly higher and high-density lipoprotein (HDL) levels were significantly lower than that of the non-OSA group. Conclusion More than half of our hypertensive patients had OSA. These two conditions often co-exist and are known as a dangerous pair. Physicians ought to have increased suspicion for early diagnosis and treatment to improve cardiovascular outcomes, reduce road traffic accidents, and improve quality of life.


Introduction
Obstructive sleep apnea (OSA) and hypertension (HTN) frequently co-exist and their association is an issue of increasing concern because they are known as a dangerous pair [1,2]. Mild to moderate OSA is present in a considerable proportion of the adult population [3]. Around 50-60% of OSA patients have daytime hypertension, whereas >30% of hypertensive patients were reported to have OSA, and OSA is likely to be an important cause of drug-resistant hypertension [4][5][6][7][8]. Studies have demonstrated a reduction in blood pressure by four to nine weeks of nasal continuous airway pressure in OSA patients [9,10].
In patients with moderate-to-severe OSA, repeated episodes of hypoxia and reoxygenation lead to inflammation and oxidative stress, and accelerate the development of atherosclerosis [11,12]. The exact mechanism behind the susceptibility to hypertension in OSA patients is not clear [12]. Patients with OSA often have impaired social life and depression and are more often involved in accidents. The increased risk of cardiovascular mortality in OSA is independent of other known risk factors such as obesity. OSA may have a synergistic role to play with other traditional and newer risk factors for the development of hypertension [13,14]. Males and females may have different risks due to differential risk factor patterns. This study was conducted with the aim to study the prevalence of OSA in hypertensive patients. Our study was designed as a cross-sectional observational study, conducted in the Department of Medicine at a tertiary care center in Northern India over one year. Hypertensive patients of age ≥ 18 years, willing and able to provide consent, were enrolled in the study.

Statistical analysis
The Statistical Package for Social Sciences (SPSS) version 21.0 statistical analysis software (IBM Corp., Armonk, NY) was used for statistical analysis. The group of continuous variables was compared by the student's t-test for analysis of variance (ANOVA) and discrete data were analyzed using the chi-square test.
The values were represented in number (%) and mean±SD. The level of significance p-value of ≤0.5 was considered significant.

Ethical approval
The present study was approved by the institutional ethical committee of King George's Medical University and was not supported by any funding agency.

Results
A total of 179 hypertensive patients fulfilling the inclusion criteria were enrolled in the study after obtaining their consent. All subjects were administered the STOP-BANG questionnaire to qualify for the polysomnography. Out of 179 cases, 42 (23.5%) cases had a STOP-BANG score ≤2, had very less risk of obstructive sleep apnea, and did not qualify for polysomnography; the rest (137; 76.5%) cases had a STOP-BANG score of ≥3 and were subjected to polysomnography ( Table 1).  Out of 137 cases who underwent polysomnography, 42 had an AHI score of <5.0, and the rest (95) had an AHI score of ≥5 ( Table 2). Only these 95 cases were diagnosed as OSA. A trend of increase in the AHI score with an increase in the STOP-BANG score was observed. A minimum AHI score was found for cases with the STOP-BANG score of 3 (3.51±2.74), which subsequently increased to 61.08±17.23 for a STOP-BANG score of 8. The association between the AHI score and the STOP-BANG score was found to be significant statistically ( Table 3 and Figure 1).    After administration of the STOP-BANG questionnaire and thereafter polysomnography of screened cases, 84 hypertensive cases had either a STOP-BANG score of ≤2 or a score of ≥3 but an AHI score <5 was not found to have the risk of OSA. Rest 95 (53.1%) cases having STOP-BANG score ≥3 and AHI score ≥5 were diagnosed as OSA. Thus the prevalence of OSA in hypertensive cases (N=179) was 53.1% ( Table 4). The severity of OSA cases is shown in Table 5   The age of hypertensive cases in our study ranged from 18 to 78 years and the mean age was 52.07±11.40 years. The mean age of OSA cases (52.34±11.40 years) was found to be slightly higher than that of non-OSA cases (51.73±11.88 years) but this difference was not found to be statistically significant. In lower age groups, i.e. up to 40 years, the proportion of non-OSA cases was higher as compared to OSA cases while among the higher age group, the proportion of OSA cases was higher as compared to non-OSA. This association was also not found to be significant statistically. Out of 179 cases enrolled in the study, 110 (61.5%) were males and the rest were females. The majority of the OSA cases were males (73.7%) while the majority of non-OSA cases were females (52.4%). This difference was found to be significant statistically. No significant association of severity of OSA was observed either with age or gender. OSA cases, as compared to non-OSA hypertensive cases, had significantly higher height, weight, and BMI. However, the association between the severity of OSA and anthropometric parameters was not found to be significant statistically (  Out of 179 hypertensive cases, only three (1.7%) were not taking any treatment for hypertension, as they were newly detected and all cases were having OSA. Out of 176 taking medications, the majority (93.75%) of them had controlled hypertension. The proportion of cases with uncontrolled hypertension was higher among OSA as compared to non-OSA (11.5% vs. 1.2%). This difference was found to be statistically significant (p=0.017). Uncontrolled hypertension cases were having a significantly higher proportion of cases of severe OSA as compared to mild and moderate OSA (20.0% vs. 3.6% & 0.0%) (p=0.016). Patients having OSA were taking more medications for hypertension than non-OSA cases but the difference was not found to be statistically significant. The association of the number of medications with the severity of OSA was also not found statistically significant. Though the duration of hypertension was higher among non-OSA cases (5.81±5.02 years) as compared to OSA cases (5.30±4.54 years), this difference was not found to be statistically significant (p=0.477).
All the OSA cases had a history of snoring as compared to only 36.9% of non-OSA; this difference was found to be significant statistically (p<0.001). Only 14.7% of OSA cases and 82.1% of non-OSA cases felt energetic, the rest complained of tiredness. The difference in the proportion of cases with complaints of tiredness was significantly higher in the OSA group as compared to the non-OSA group (85.3% vs. 17.9%). Complaints of tiredness were observed in a higher proportion of moderate and severe OSA patients as compared to mild OSA (95.5% & 95.6% vs. 60.7%); this difference was found to be significant statistically (p<0.001).
Significant differences among OSA and non-OSA cases were observed for triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. The HDL levels of OSA cases were found to be significantly lower than that of non-OSA cases. Triglyceride and LDL levels in OSA cases were found to be significantly higher than that in non-OSA cases. No significant association between the severity of OSA and the above parameters was found.

Discussion
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder affecting the majority of the adult population. The major risk factors for OSA are obesity, male sex, advancing age, and elevated blood pressure. OSA is a potential cause of resistant hypertension. A major portion of hypertensive patients have concomitant OSA, but they usually remain undiagnosed due to a lack of awareness and inadequate screening. Most of the studies related to the prevalence of OSA in hypertension are from outside India [14].
In the present study, we screened 179 hypertensive cases using the STOP-BANG questionnaire for OSA. Out of these, 137 (76.5%) cases having a STOP-BANG score of ≥3 were subjected to polysomnography. Out of those who underwent polysomnography, 42 (30.7%) had an AHI score of <5.0, and the rest 95 (69.3%) had an AHI of ≥5. Only these 95 cases were diagnosed as OSA. Thus, the prevalence of OSA in our hypertensive patient was 53.1%. A trend of increase in the AHI score with an increase in the STOP-BANG score was observed. The association between the AHI score and the STOP-BANG score was found to be significant statistically. A similar study was conducted by Ricardo Luiz de Menezes Duarte et al. (2017). In their study, they found that an increase in the score was paralleled by an increase in specificity for all AHI cut-off points. According to their study, the STOP-BANG questionnaire is the best screening test for OSA [15]. A cross-sectional analysis by Elizabeth S. Muxfeldt et al. was of 422 resistant hypertension (RHT) (31.3% men; mean age = 62.4 ± 9.9 years) submitted to full-night polysomnography. RHT patients had a very high prevalence of OSA (82%) and moderate/severe OSA (55%) [16].
The mean age of the patients enrolled in our study was 52+11.4 years. The mean age of the OSA cases (52.34+11.40) was slightly higher than non-OSA cases (51.73+11.88). In the study by Cristopher John Worsnop et al., the mean age of the patients was 58+2.1 and 60.9+2 among untreated hypertensives and treated hypertensives, respectively, which correlates with our study [5]. Our study showed that higher age is a significant risk factor for OSA.
Out of 179 cases enrolled in the study, 110 (61.5%) were males and the rest were females. The majority of the OSA cases were males (73.7%) while the majority of non-OSA cases were females (52.4%). This difference was found to be significant statistically. This is supported by Vahid Mohsenin et al., who studied 736 OSA cases, in which males were more than females. This study was also supported by the study of Hedner et al. on 141 patients with hypertension in primary health care, which showed a higher prevalence of OSA in males than females, concluding that there was an independent association between hypertension and OSA in males but not in females [17,18].
Out of 179 hypertensive cases, 138 (93.7% of OSA and 58.3% of non-OSA cases) were overweight (BMI >25 kg/m 2 ). The mean weight of the OSA group (84.45±17.17 kg) had a significantly higher weight as compared to the non-OSA group (64.26+12.00 kg). An increase in the proportion of overweight patients was also observed with an increase in the severity of OSA, i.e. mild (85.7%), moderate (90.9%), and severe (100.0%). In the study, OSA is associated with higher BMI, and the severity of OSA also increases with an increase in BMI. Thus, it can be esteemed that the prevalence, as well as the severity of OSA, increases with increasing BMI. This was supported by Gary D. Foster. et al, in whose study over 86% of participants had OSA with an AHI of ≥5 events/h. The mean AHI was 20.5 ± 16.8 events/h. Severe OSA was more in individuals with a higher BMI (odds ratio 1.1; 95% CI 1.0-1.2; P = 0.03) [19].
Out of 179 hypertensive cases, only three (1.7%) were not taking any treatment for hypertension, as they are newly diagnosed and all three cases had OSA. Out of 176 taking medications, the majority (93.75%) of them had controlled hypertension. The proportion of cases with uncontrolled hypertension was higher among OSA as compared to non-OSA (11.5% vs. 1.2%). This difference was found to be significant statistically (p=0.017). Most of these uncontrolled hypertension cases had a significantly higher proportion of cases of severe OSA as compared to mild and moderate OSA (p=0.016). Patients who had OSA were taking more medications for hypertension than non-OSA cases but the difference was not found statistically significant. The association of the number of medications with the severity of OSA was also not found to be significant statistically.  [20].
In our study, all the OSA groups had a history of snoring as compared to only 36.9% of the non-OSA group. This difference was found to be significant statistically (p<0.001). Our study is supported by Thikriat S. Al-Jewair et al., who studied a total of 200 consecutive female and male dental patients. Habitual snoring was present in 18.2% of the females and 81.8% of the males (p<0.05). Breathing pauses during sleep more than once a week occurred in 9% (n=17) of the sample. Of the males, 78.3% were at high risk of OSA as compared with 21.7% of the females [21].

Conclusions
More than half of the patients enrolled in the study had OSA. Male patients who had increased weight, BMI, and uncontrolled hypertension have a much more chance of developing severe OSA. As the prevalence of OSA is significantly higher among hypertensive patients, these patients should be screened easily by a simple questionnaire and subsequently may be subjected to polysomnography for early diagnosis and treatment to reduce morbidity and mortality and improve the quality of life.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. King George's Medical University U.P., Institutional Ethics Committee issued approval 828/Ethics/19. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.